Purpose: Ernst von Glasersfeld’s question concerning the relationship between scientific/ rational knowledge and the domain of wisdom and how these forms of knowledge come about is the starting point. This article aims at developing an epistemological as well as methodological framework that is capable of explaining how profound change can be brought about in various contexts, such as in individual cultivation, in organizations, in processes of radical innovation, etc. This framework is based on the triple-loop learning strategy and the U-theory approach, which opens up a perspective on how the domains of scientific/rational knowledge, constructivism, and wisdom could grow together more closely. Design/Structure: This article develops a strategy which is referred to as “tripleloop learning,” which is not only the basis for processes of profound change, but also brings about a new dimension in the field of learning and knowledge dynamics: the existential realm and the domain of wisdom. A concrete approach that puts into practice the tripleloop learning strategy is presented. The final section shows, how these concepts can be interpreted in the context of the constructivist approach and how they might offer some extensions to this paradigm. Findings: The process of learning and change has to be extended to a domain that concerns existential issues as well as questions of wisdom. Profound change can only happen if these domains are taken into consideration. The tripleloop learning strategy offers a model that fulfills this criterion. It is an “epistemo-existential strategy” for profound change on various levels. Conclusions: The (cognitive) processes and attitudes of receptivity, suspension, redirecting, openness, deep knowing, as well as “profound change/innovation from the interior” turn out to be core concepts in this process. They are compatible with constructivist concepts. Von Glasersfeld’s concept of functional fitness is carried to an extreme in the suggested approach of profound change and finds an extension in the existential domain. Key words: Double-loop learning, individual cultivation, (radical) innovation, knowledge creation, knowledge society, personality development, presencing, profound change, triple-loop learning, U-theory, wisdom